Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique, Université Montpellier 2, Université Montpellier 1, Montpellier, France.
PLoS One. 2010 Jun 21;5(6):e11235. doi: 10.1371/journal.pone.0011235.
The c-fos proto-oncogene is an archetype for rapid and integrative transcriptional activation. Innumerable studies have focused on the canonical promoter, located upstream from the transcriptional start site. However, several regulatory sequences have been found in the first intron.
METHODOLOGY/PRINCIPAL FINDINGS: Here we describe an extremely conserved region in c-fos first intron that contains a putative TATA box, and functional TRE and CRE sites. This fragment drives reporter gene activation in fibroblasts, which is enhanced by increasing intracellular calcium and cAMP and by cotransfection of CREB or c-Fos/c-Jun expression vectors. We produced transgenic mice expressing a lacZ reporter controlled by the intronic promoter. Lac Z expression of this promoter is restricted to the developing central nervous system (CNS) and the mesenchyme of developing mammary buds in embryos 12.5 days post-conception, and to brain tissue in adults. RT-QPCR analysis of tissue mRNA, including the anlage of the mammary gland and the CNS, confirms the existence of a novel, nested mRNA initiated in the first intron.
CONCLUSIONS/SIGNIFICANCE: Our results provide evidence for a novel, developmentally regulated promoter in the first intron of the c-fos gene.
c-fos 原癌基因是快速和综合转录激活的原型。无数研究都集中在位于转录起始位点上游的典型启动子上。然而，在第一个内含子中已经发现了几个调节序列。
方法/主要发现：在这里，我们描述了 c-fos 第一个内含子中一个非常保守的区域，该区域包含一个假定的 TATA 盒和功能性 TRE 和 CRE 位点。该片段可在成纤维细胞中驱动报告基因的激活，通过增加细胞内钙和 cAMP 以及共转染 CREB 或 c-Fos/c-Jun 表达载体可增强其活性。我们制备了表达受内含子启动子控制的 lacZ 报告基因的转基因小鼠。该启动子的 lacZ 表达仅限于发育中的中枢神经系统（CNS）和胚胎 12.5 天的乳腺芽发育中的间充质，以及成年脑组织。对包括乳腺原基和 CNS 在内的组织 mRNA 的 RT-QPCR 分析证实了一种新型的、嵌套的 mRNA 存在于第一个内含子中。
结论/意义：我们的结果为 c-fos 基因第一个内含子中存在一个新型的、发育调控的启动子提供了证据。
